Irradiation of Large Lung Tumors or Two or More Lung Metastases Simultaneously (VOLUMES)

VOLUMES Treatment of Larger Tumor Volumes or ≥ 2 Lung Tumors Simultaneously in Lung Cancer Patients Using SBRT in a Mean-lung Dose Escalation Study

Treatment of larger tumor volumes or ≥ 2 lung metastases simultaneously in lung cancer patient using Stereotactic Body Radiation Therapy (SBRT) in a mean-lung dose escalation study.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Metastatic Lung Cancer
• Intervention / Treatment: Radiation: Stereotactic Body Radiotherapy (SBRT); Radiation: Stereotactic Body Radiotherapy (SBRT)

Detailed Description

A phase I/II multicenter trial will be conducted in patients with medically inoperable with peripheral non small cell lung cancer (NSCLC) > 5 cm without lymph node involvement (group A) or medically with ≥ 2 or more lung metastases (group B). Radiation pneumonitis is expected to be dose-limiting in these patients and there is evidence that the incidence is predicted by the mean lung dose (MLD). The MLD escalation will be performed separately in both patient groups, using a time-to-event continual reassessment method (TITE-CRM). All patients will receive 3-5 fractions SBRT to the lung tumor(s), with a minimum mean PTV dose ≥ 42 Gy. Fraction size may be downscaled based on the MLD constraint.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Prinses Margaret Hospital
• Germany
  • Bayern
    • Würzburg, Bayern, Germany, DE-97080
      • Universitatsklinikum Wurzburg
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • NKI-AvL
• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48076
      • Beaumont Hospital, Royal Oak
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, PA 19107
      • Thomas Jefferson University/ Kimmel Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for group A and B:

• Weight loss < 10% in the last three months.
• WHO-performance status ≤ 2
• Medical inoperable patients or patients refusing surgery.
• Chemotherapy is allowed in neoadjuvant and adjuvant setting, with exclusion of the period 4 weeks pre-SBRT and 6 weeks post-SBRT.
• Before patient registration, written informed consent must be given according to ICH/GCP, national and local regulations.

Risk group A specification:

• NSCLC (Cytological or histological proven) patients with peripheral tumors >5 cm with tumor staging cT2bN0M0 or cT3N0M0 (chest wall infiltration is no exclusion criteria, as long as the tumor diameter is > 5 cm).
• Single peripheral lung metastasis in inoperable patients with a diameter of > 5 cm. In case of first presentation of metastatic disease, cytological or histological proof is obligated.
• In patients without cytological or histological confirmation of NSCLC, a growing FDG-PET positive lesion (SUV >5) is accepted if a contra-indication for invasive diagnostic examination (or refusal) is present.

Risk group B specification:

• Patients with ≥ 2 simultaneous peripheral lung metastases ≤ 5 cm of any origin at any location in the lung.
• In case of first presentation of metastatic disease, cytological or histological proof is obligated. This is not necessary in case of a history of an already proven disseminated disease.
• Patients having ≥ 2 peripheral lung metastases without unacceptable dose overlap.

Exclusion Criteria:

• Patients with central tumors
• Pancoast tumors
• Prior radiotherapy treatment to the thorax
• Patients receiving any systemic treatment during SBRT
• Pregnant patients
• Patients previously treated with adriamycin agents in case of heart involvement within the treatment field.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SBRT group A; escalate MLD in medically inoperable patients with tumors larger than 5 cm in diameter (primary or solitary metastases)	Radiation: Stereotactic Body Radiotherapy (SBRT); 3-5 fractions within 10-14 days; Other Names: Stereotactic Body Radiotherapy; Radiation: Stereotactic Body Radiotherapy (SBRT); 3-5 fractions per tumor within one treatment session or sequential within one month; Other Names: Stereotactic Body Radiotherapy
Experimental: SBRT group B; Escalate the MLD in patients with ≥ 2 lung metastases	Radiation: Stereotactic Body Radiotherapy (SBRT); 3-5 fractions within 10-14 days; Other Names: Stereotactic Body Radiotherapy; Radiation: Stereotactic Body Radiotherapy (SBRT); 3-5 fractions per tumor within one treatment session or sequential within one month; Other Names: Stereotactic Body Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MLD	The assessment of the maximum mean lung dose that can be safely treated with SBRT and that is associated with a 20% probability of the DLT.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
loco-regional control	Determine the local control and regional control as a function of the mean lung dose, the largest toxicity effects as a function of the MLD and the overall survival.	4 years
overall survival	Determine the local control and regional control as a function of the mean lung dose, the largest toxicity effects as a function of the MLD and the overall survival.	5 years
Quality of life assessment	valuate the increase or decrease of physical discomfort.	2 years

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Investigators: Principal Investigator: Heike Peulen, MD, the Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2011
• Primary Completion (Actual): October 31, 2017
• Study Completion (Actual): October 31, 2017

Study Registration Dates

• First Submitted: February 21, 2012
• First Submitted That Met QC Criteria: March 2, 2012
• First Posted (Estimate): March 5, 2012

Study Record Updates

• Last Update Posted (Actual): June 27, 2019
• Last Update Submitted That Met QC Criteria: June 26, 2019
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: lung; SBRT; toxicity; MLD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: M11VOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No